Autocrine, paracrine and juxtacrine signaling by EGFR ligands

Amar B. Singh, Raymond C. Harris

Research output: Contribution to journalReview articlepeer-review

305 Scopus citations


Receptor and cytoplasmic protein tyrosine kinases play prominent roles in the control of a range of cellular processes during embryonic development and in the regulation of many metabolic and physiological processes in a variety of tissues and organs. The epidermal growth factor receptor (EGFR) is a well-known and versatile signal transducer that has been highly conserved during evolution. It functions in a wide range of cellular processes, including cell fate determination, proliferation, cell migration and apoptosis. The number of ligands that can activate the EGF receptor has increased during evolution. These ligands are synthesized as membrane-anchored precursor forms that are later shed by metalloproteinase-dependent cleavage to generate soluble ligands. In certain circumstances the membrane anchored isoforms as well as soluble growth factors may also act as biologically active ligands; therefore depending on the circumstances these ligands may induce juxtacrine, autocrine, paracrine and/or endocrine signaling. In this review, we discuss the different ways that EGFR ligands can activate the receptor and the possible biological implications.

Original languageEnglish (US)
Pages (from-to)1183-1193
Number of pages11
JournalCellular Signalling
Issue number10
StatePublished - Oct 2005
Externally publishedYes


  • Autocrine
  • Epidermal growth factor receptor
  • Heparin-binding EGF like growth factor
  • Juxtacrine
  • TGF-α

ASJC Scopus subject areas

  • Cell Biology


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